Field of the Invention
The present invention relates to a recombinant (chimera) baculovirus and a vaccine composition thereof.
Description of the Related Art
HPV (human papillomavirus) is a causative factor in the development of cervical cancer which occupies approximately 12% of global women's cancer. Incidence frequency and mortality of cervical cancer is higher enough to be at a rate of one person per 2 min in the world (Vaccine 24: 5235-5244 (2006)). Presently, about 100 types of HPV have been identified. Of them, HPV type 16 and HPV type 18 classified as high risk group have been found in the tissue of cervical cancer at a ratio of not less than 70% (Vaccine 22: 3004-3007 (2004)).
To modulate cervical cancer, an effective vaccine development for HPV infection has been attempted. First of all, there is urgently demanded a vaccine development for preventing cervical cancer.
HPV L1 protein as VLPs (virus like particles) has inherent self-assembly potential, allowing to form external envelopes without viral genome. It has been reported that VLP contributes to sufficient induction of immune responses to produce a neutral antibody having higher titer (Journal of Virology 81 (24): 13927-13931 (2007); Virology 321: 205-216 (2004); Journal of Medical Virology 80: 841-846 (2008)).
For efficient gene delivery in vivo, gene delivery systems have been developed using numerous viral vectors. For the purpose of gene therapy, viral vectors such as retrovirus and adenovirus are utilized to deliver HPV16L1 gene to an animal host (Science 260 (5110): 926-932 (1993)). However, utility of these viruses cause several drawbacks including: (a) virus proliferation in a replication-dependent manner; (b) cytotoxicity; (c) induction of early immune responses; and (d) expression of undesired viral genes.
By contrast, a baculovirus transfer vector has important advantages as follows: (a) insertion of a foreign gene having a relatively large size; and (b) post-translation processing due to use of insect cells (higher eukaryotic cells). The latter advantage is very crucial in the senses that the biological and immunological activity of a recombinant protein expressed by using a baculovirus transfer vector are almost equivalent to those of original protein compared with protein produced in prokaryote, E. coli. In addition, baculovirus has been known to be a biologically safe virus because its replication is impossible in animal cells and it induces no cytotoxicity (Virology 125: 107-117 (1983); Hum. Gene Ther. 7: 1937-1945 (1996); Proc. Natl. Acad. Sci. USA 96: 127-132 (1999); Trends Biotechnol. 20: 173-180 (2002)). It has been known that the replication of AcNPV (Autographa californica nuclear polyhedrosis virus) belonging to be an insect virus group is also impossible in a variety of animal cells, whereas it is possible to deliver a gene into cells through its infection (Proc. Natl. Acad. Sci. USA 92: 10099-10103 (1995); Proc. Natl. Acad. Sci. USA 93: 2348-2352 (1996)). Previously, it was reported that a specific gene in AcNPV genome could be highly expressed in animal cells where it is controlled by an animal promoter (Journal of Virology, 76 (11): 5729-5736 (2002); Vaccine 26 (20): 2451-2456 (2008)).
Recently, several studies tried to increase a gene transfer efficiency by introducing Env of other viruses onto the surface of baculovirus, for example including diverse reports obtaining higher gene transfer efficiency by introduction of a VSV envelope G protein onto the surface of baculovirus (Journal of Virology, 78 (16): 8663-8672 (2004); Journal of Urology 250 (2): 276-283 (2006); Biochemical and Biophysical Research Communications 289 (2): 444-450 (2001); Journal of Virology 75 (6): 2544-2556 (2001)), or by adding a gp64 protein on virus surface (Human Gene Therapy, 14 (1): 67-77 (2003)). In addition, vaccination using a baculovirus vector was known to induce immune responses against a hemagglutinin glycoprotein of influenza virus (Journal of Immunology, 171: 1133-1139 (2003)).
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.